The overall objective of this Center of Excellence for Research on Complementary and Alternative[unreadable] Medicine in Alzheimer's disease application is to identify bioactive grape-derived polyhenols in AD[unreadable] prevention and/or therapy in the Tg2576 mouse model of Alzheimer's disease-type Ap neuropathology and[unreadable] cognitive deterioration. The proposed studies in this application are based on our hypothesize that selective[unreadable] bioactive grape-derived polyphenols protects against the onset and progression of AD-type cognitive[unreadable] deterioration by inhibiting the generation of A/7peptides from the amyloid precursor protein. We will test this[unreadable] hypothesis by using bio-guided fractionation methodologies to generate polyphenol preparations with[unreadable] progressively less complexity from Cabernet Sauvignon and from Concord purple grape juice that will exert A0-[unreadable] lowering activity in the Tg2576 AD mouse model. We will continue to explore the efficacy of ApMowering[unreadable] polyphenol preparations to attenuate the onset and progression of AD-type cognitive deterioration in Tg2576[unreadable] mice and to clarify the mechanisms of action.[unreadable] The proposed studies in this application will complement the other Research Projects in this Center[unreadable] application and elucidate general mechanisms by which grape-derived polyphenolics may blunt age-related[unreadable] Alzheimer's disease, especially in a growing population affected by mild cognitive impairment that is at high[unreadable] risk for AD. Outcomes of the proposed studies will likely result in the development of selective grape-derived[unreadable] polyphenolic compounds as lead compounds for clinical testing in Alzheimer's disease[unreadable]